scholarly journals A Comparison of Oral and Intravenous Mouse Models of Listeriosis

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 13 ◽  
Author(s):  
◽  

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well as the development of a foodborne route of transmission has reignited interest in studying oral models of listeriosis. In this review, we analyze previously published reports to highlight both the similarities and differences in tissue colonization and host response to infection using either oral or i.v. inoculation.

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.


2008 ◽  
Vol 82 (9) ◽  
pp. 4331-4342 ◽  
Author(s):  
Christopher C. Kemball ◽  
Stephanie Harkins ◽  
J. Lindsay Whitton

ABSTRACT Previous studies have suggested that coxsackievirus B (CVB) activates CD8+ T cells in vivo, but the extent of this activation and the antigen specificity of the CD8+ T cells remain uncertain. Furthermore, CVB-induced CD4+ T-cell responses have not been carefully investigated. Herein, we evaluate CD8+ and CD4+ T-cell responses both in a secondary lymphoid organ (spleen) and in peripheral tissues (heart and pancreas), using a recombinant CVB3 (rCVB3.6) that encodes well-characterized CD8+ and CD4+ T-cell epitopes. Despite reaching high levels in vivo, rCVB3.6 failed to trigger a marked expansion of CD8+ or CD4+ T cells, and T-cell activation was surprisingly limited. Furthermore, epitope-specific effector functions could not be detected using highly sensitive in vivo and ex vivo assays. Moreover, major histocompatibility complex (MHC) class I tetramer analysis indicated that our inability to detect CVB3-specific CD8+ T-cell responses could not be explained by the cells being dysfunctional. In contrast to naïve T cells, epitope-specific memory CD8+ and CD4+ T cells proliferated markedly, indicating that both of the rCVB3.6-encoded epitopes were presented by their respective MHC molecules in vivo. These data are consistent with the observation that several CVB3 proteins can limit the presentation of viral epitopes on the surface of infected cells and suggest that the level of MHC/peptide complex is sufficient to trigger memory but not naïve T cells. Finally, our findings have implications for the biological significance of cross-priming, a process thought by some to be important for the induction of antiviral CD8+ T-cell responses.


2016 ◽  
Vol 35 (1) ◽  
pp. 23-31 ◽  
Author(s):  
John T. Martin ◽  
Dong Hwa Kim ◽  
Andrew H. Milby ◽  
Christian G. Pfeifer ◽  
Lachlan J. Smith ◽  
...  

2010 ◽  
Vol 37 (7) ◽  
pp. 853-860 ◽  
Author(s):  
Kazuhiko Yanamoto ◽  
Katsushi Kumata ◽  
Masayuki Fujinaga ◽  
Nobuki Nengaki ◽  
Makoto Takei ◽  
...  

2017 ◽  
Vol 16 ◽  
pp. 153601211771263 ◽  
Author(s):  
Benjamin L. Franc ◽  
Sam Goth ◽  
John MacKenzie ◽  
Xiaojuan Li ◽  
Joseph Blecha ◽  
...  

2012 ◽  
Vol 5 ◽  
pp. IDRT.S10652
Author(s):  
Takashi Irie ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Ronald N. Harty

The M40 VSV recombinant was engineered to contain overlapping PTAP and PPxY L-domain motifs and flanking residues from the VP40 protein of Ebola virus. Replication of M40 in cell culture is virtually indistinguishable from that of control viruses. However, the presence of the Ebola PTAP motif in the M40 recombinant enabled this virus to interact with and recruit host Tsg101, which was packaged into M40 virions. In this brief report, we compared replication and the pathogenic profiles of M40 and the parental virus M51R in mice to determine whether the presence of the Ebola L-domains and flanking residues altered in vivo characteristics of the virus. Overall, the in vivo characteristics of M40 were similar to those of the parental M51R virus, indicating that the Ebola sequences did not alter pathogenesis of VSV in this small animal model of infection.


Virology ◽  
2014 ◽  
Vol 448 ◽  
pp. 65-73 ◽  
Author(s):  
Rico Blochmann ◽  
Christoph Curths ◽  
Cheick Coulibaly ◽  
Klaus Cichutek ◽  
Reinhard Kurth ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document